STIMULUS-MDS1 Trial: Sabatolimab and HMA Falls Short in Higher-Risk MDS

Primary results from the ongoing phase 2 STIMULUS-MDS1 trial (ClinicalTrials.gov Identifier: NCT03946670) showed that sabatolimab (MBG453), a novel TIM3-targeted immunotherapy, plus HMA did not significantly improve PFS compared with placebo (11.1 months vs. 8.5 months; P =.102) in patients with intermediate-risk, high-risk, and very-high risk MDS.³

The rate of complete response (CR) plus partial remission and hematologic improvement was 49.2% with sabatolimab-HMA and 37.1% with placebo. The CR rate was 23.1% and 21.0%, respectively. The median duration of CR was 18.0 months and 9.2 months, respectively. The median OS was 19.0 months and 18.0 months, respectively (HR, 0.905).

“While improvements in the primary endpoint measures were not statistically significant, longer assessment may suggest a delayed onset benefit for patients who were given sabatolimab,” said study presenter Amer M. Zeidan, MD, of Yale University in New Haven.

“The ongoing phase 3 STIMULUS-MDS2 trial with a primary endpoint of OS has completed accrual and will definitively determine on the impact of sabatolimab in higher-risk MDS patients,” he concluded.

SINTRA-REV Trial: Low-Dose Lenalidomide Lowers Risk of Transfusion Dependency, Improves Responses

Final results from the phase 3 SINTRA-REV trial (ClinicalTrials.gov Identifier: NCT01243476) showed that, compared with placebo, low-dose lenalidomide prolonged time to transfusion, lowered the risk of transfusion dependency, and demonstrated no increase in progression rate or clonal evolution in patients with low-risk MDS.

At a median follow-up of 5.05 years, low-dose lenalidomide lowered the risk of transfusion dependency by 69.8% (HR, 0.302; P =.005). With respect to erythroid response, patients treated with low-dose lenalidomide had a 77.8% response compared with 0% for placebo. In terms of cytogenetic response, patients in the lenalidomide group had a response of 94.1% compared with 0% for placebo.

“The median time to transfusion dependency was not reached for patients who received lenalidomide compared with 11.6 months in those who received placebo,” said study presenter Maria Diez-Campelo, MD, of Hospital Universitario de Salamanca-IBSAL in Salamanca, Spain.

The rate of grade 3/4 neutropenia was 44.7% in patients treated with low-dose lenalidomide and 4.8% in those who received placebo. However, the researchers noted that low-dose lenalidomide did not cause clinically relevant neutropenia.

“Based on the results, we confirm that early treatment with low-dose lenalidomide prolonged the time and reduced the risk of transfusion dependency, with promising responses and an acceptable safety profile,” Dr Diez-Campelo concluded.

Disclosures: The ASCERTAIN trial was sponsored by Astex Pharmaceuticals. The MEDALIST trial was sponsored by Celgene and Acceleron Pharma. STIMULUS-MDS1 was sponsored by Novartis. The SINTRA-REV trial was co-sponsored by Fundación General de la Universidad de Salamanca and Celgene. Please see the original references for a full list of disclosures.

References

1. Savona MR, McCloskey JK, Griffiths EA, et al. Prolonged survival in bi-allelic TP53-mutated (TP53mut) MDS subjects treated with oral decitabine/cedazuridine in the ascertain trial (ASTX727-02). Presented at ASH 2022; December 10-13, 2022. Abstract 854.

2. Santini V, Fenaux P, Zeidan AM, et al. Overall survival and progression-free survival of patients following luspatercept treatment in the MEDALIST trial. Presented at ASH 2022; December 10-13, 2022. Abstract 1774.

3. Zeidan AM, Ando K, Rauzy O, et al. Primary results of stimulus-MDS1: a randomized, double-blind, placebo-controlled phase II study of TIM-3 inhibition with sabatolimab added to hypomethylating agents (HMAs) in adult patients with higher-risk myelodysplastic syndromes (MDS). Presented at ASH 2022; December 10-13, 2022. Abstract 853.

4. Cadenas FL, Lumbreras E, Gonzalez T, et al. Evaluation of lenalidomide (len) vs placebo in non-transfusion dependent low risk del(5q) MDS patients. Final results of Sintra-REV phase III international multicenter clinical trial. Presented at ASH 2022. December 10-13, 2022. Abstract 460.